FDA Approves Utebzi (tebipenem pivoxil) for Adults with Complicated Urinary Tract Infections

GSK plc (LSE/NYSE: GSK) and Spero Therapeutics (Nasdaq: SPRO)   announced  the US Food and Drug Administration (FDA)  approval of  Utebzi, an oral antibiotic for the treatment of complicated urinary tract infections (cUTIs) including pyelonephritisa, caused by certain susceptible pathogensb in adult patients who have limited or no alternative oral treatment options. This is the first and only oral carbapenem antibiotic approved for these patients. This approval is a result of GSK’s development and exclusive global licensing agreement (excluding select Asian territories) with Spero Therapeutics.4

• First and only oral carbapenem antibiotic approved in the US
• Approval based on PIVOT-PO trial demonstrating non-inferiority compared to intravenous treatment1
• More than 3 million cases of cUTIs are treated annually in the US2 with up to a third of patients impacted by resistant infections3

There are more than 3 million cases of cUTI in the US annually and treatment failure impacts up to 34% of patients.2,3 Often caused by multidrug-resistant pathogens,5 these infections account for over $6 billion per year in healthcare costs.6 Carbapenems are the standard treatment for severe or resistant infections, but until now have only been available through intravenous administration7, increasing hospital resource use and reducing patients’ quality of life.8 Tebipenem pivoxil offers the potential for an effective oral alternative taken outside of a hospital setting.

Tony Wood, Chief Scientific Officer, GSK, said: “With antibiotic resistance continuing to rise, patients and healthcare professionals need new treatment options. The approval of Utebzi provides the first and only oral carbapenem antibiotic for appropriate adults with complicated UTIs, a solution that could help reduce reliance on hospital-based intravenous care and support efforts to address resistant infections.”

Dr. Bilal Chughtai, Chief of Urology at Plainview Hospital, Northwell Health and Associate Professor of Urology at the Zucker School of Medicine at Hofstra/Northwell, said: “For patients with complicated urinary tract infections (cUTIs) and their caregivers, this approval is a major milestone as today’s standard of care places a serious burden on them and hospitals. A new effective oral treatment offering an alternative option to intravenous care has the potential to enable more treatment in the outpatient settings with the ambition to improve their experience.”

Esther Rajavelu, President and Chief Executive Officer, Spero Therapeutics added: “The FDA approval of tebipenem pivoxil marks the culmination of more than a decade of dedication from our team, partners, and, most importantly, the patients who placed their trust in this program. We are proud to reach this important milestone. Through our partnership with GSK, we look forward to this much-needed oral treatment option reaching cUTI patients to help reduce the burden of the disease.”

This approval is supported by positive results from the PIVOT-PO phase III trial, which demonstrated non-inferiority of tebipenem pivoxil compared to intravenous imipenem-cilastatin in hospitalised patients with cUTI, including pyelonephritis, based on the overall response (composite of clinical cure plus microbiological eradication) at the test of cure visit. Tebipenem pivoxil (oral, 600 mg) achieved a 58.5% overall success rate (261/446 participants) compared to 60.2% overall success rate (291/483 participants) for imipenem-cilastatin (intravenous, 500 mg) (adjusted treatment difference: −1.3%; 95% CI: −7.5%, 4.8%).

The safety profile of tebipenem pivoxil was generally similar to that of imipenem-cilastatin and other carbapenem antibiotics. The most frequently reported adverse events (in ≥3% of patients) were diarrhoea and headache; these events were all mild or moderate and non-serious.1

Tebipenem pivoxil is anticipated to be made available to US patients by the end of 2026. With this approval, GSK builds on recent advances in its growing anti-infectives portfolio.

This approval confirms the successful and productive collaboration between GSK and Spero Therapeutics. The development of tebipenem pivoxil has been supported in part with federal funds from the US Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA), under contract numbers HHSO100201800015C and HHSO100201300011C.

a Pyelonephritis is a specific type of UTI that has travelled up the urinary tract to infect one or both kidneys.

b Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae species complex, Klebsiella oxytoca, and Enterococcus faecalis.

About tebipenem pivoxil

Tebipenem pivoxil was developed in collaboration with Spero Therapeutics4 for the treatment of cUTIs, including pyelonephritis. In September 2022, GSK entered into an exclusive license agreement with Spero Therapeutics for the development and commercialisation in all markets, except certain Asian territories. Under this agreement, GSK sub-licensed back to Spero Therapeutics the rights and responsibility to conduct certain development work, including the PIVOT-PO phase III study. The sponsorship of the New Drug Application has been transferred to GSK. As part of the license agreement, tebipenem pivoxil has received Qualified Infectious Disease Product and Fast Track designations from the US FDA.

About the PIVOT-PO trial

The PIVOT-PO trial was a global, randomised, double-blind, pivotal, non-inferiority (NI margin: -10%) phase III trial evaluating the potential of oral tebipenem pivoxil compared to IV imipenem-cilastatin, in hospitalised adult patients with complicated urinary tract infections, including acute pyelonephritis. Patients were randomised 1:1 to receive tebipenem pivoxil (600 mg) orally every six hours, or imipenem-cilastatin (500 mg) IV every six hours, for a total of seven to ten days. Dose adjustments were made for patients with reduced renal function. Matching placebos were used to maintain blinding. The primary efficacy endpoint was composite response (combined per-patient clinical cure and microbiological response) at the test-of-cure visit (about 17 days from first dose administration of study drug) in patients with qualifying pathogens susceptible to imipenem. The trial enrolled a total of 1,690 patients, with randomisation stratified by age, baseline diagnosis (cUTI or acute pyelonephritis), and the presence or absence of urinary tract instrumentation. For further details on the trial, refer to clinicaltrials.gov identifier NCT0605984

https://en.wikipedia.org/wiki/Tebipenem_pivoxil

FDA Approves Utebzi (tebipenem pivoxil) for Adults with Complicated Urinary Tract Infections

FDA Approves Lipfendra (enlicitide) Oral PCSK9 Inhibitor to Reduce LDL-C in Adults with Hypercholesterolemia

Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced the U.S. Food and Drug Administration (FDA)   approval of  Lipfendra (enlicitide) tablets 20 mg as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH). Lipfendra is a novel macrocyclic peptide and is the first FDA-approved oral PCSK9 inhibitor shown to lower LDL-C, also known as bad cholesterol.

• At week 24 in the CORALreef Lipids and CORALreef HeFH trials, Lipfendra significantly reduced LDL-C by a placebo-adjusted 56% and 59%, respectively
• Lipfendra is a novel macrocyclic peptide that binds to PCSK9 and inhibits the interaction of PCSK9 with LDL receptors

“By harnessing the innovative science of PCSK9 inhibitors and novel macrocyclic peptide technology, Lipfendra was designed to significantly lower LDL-C in the form of a convenient once-daily pill,” said Dr. Dean Y. Li, president, Merck Research Laboratories. “This is a pivotal moment as we bring the first U.S. FDA-approved oral PCSK9 inhibitor to adults with high LDL-C, offering patients an important new option. We’re proud of our work with regulators on this rigorous and efficient review process.”

The approval is based on two Phase 3 trials from the CORALreef clinical program: CORALreef Lipids and CORALreef HeFH. In CORALreef Lipids, Lipfendra reduced LDL-C by 56% compared to placebo at week 24. A 60% decrease from baseline in LDL-C was observed with Lipfendra when biologically impossible baseline LDL-C values were removed according to revised data handling rules (post-hoc). In CORALreef HeFH, Lipfendra reduced LDL-C by 59% at week 24 compared to placebo. Results from these Phase 3 trials showed treatment with Lipfendra resulted in reductions across other atherogenic lipoproteins associated with atherosclerotic cardiovascular disease (ASCVD) risk including non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (ApoB). The safety profile of Lipfendra in CORALreef Lipids was similar to placebo. In CORALreef HeFH, the most common adverse reactions in adults with HeFH treated with Lipfendra that occurred at higher frequencies compared to placebo were diarrhea (Lipfendra 7%, placebo 2%) and dizziness (Lipfendra 9%, placebo 4%). In both trials, similar proportions of Lipfendra-treated patients and placebo-treated patients discontinued treatment because of an adverse reaction. For additional information on results from the CORALreef trials, see “Clinical data supporting FDA approval” below.

“High LDL-C is a major risk factor for atherosclerotic cardiovascular disease, which is the leading cause of death globally,” said Dr. Ann Marie Navar, a lead author of the CORALreef Lipids study and associate professor of medicine in the Division of Cardiology at UT Southwestern Medical Center. “In two Phase 3 trials, Lipfendra led to impressive reductions in LDL-C. Now, for the first time, patients have an oral PCSK9 inhibitor for LDL lowering.”

An ongoing clinical trial is studying the effect of Lipfendra on cardiovascular morbidity and mortality. It is not yet known if Lipfendra can reduce the risk of cardiovascular morbidity and mortality.

“One of the greatest opportunities to help manage the risk of ASCVD lies in the timely identification and appropriate treatment of risk factors, such as LDL-C,” said Katherine Wilemon, CEO of the Family Heart Foundation. “We are encouraged by the approval of a new oral PCSK9 inhibitor option for adults who need additional LDL-C lowering.”

Clinical data supporting FDA approval

Lipfendra was approved based on results from two pivotal Phase 3 trials from the CORALreef clinical trial program:

• At week 24, in the CORALreef Lipids trial, treatment with Lipfendra resulted in:
  • A statistically significant and clinically meaningful reduction in LDL-C of 56% compared to placebo at week 24 (95% CI: -61, -51; p<0.001), with a reduction from baseline (primary endpoint) in LDL-C of 57% for Lipfendra compared to an increase of 3% for placebo;
  • When LDL-C values ≤0 were removed according to revised data handling rules (post-hoc), a statistically significant and clinically meaningful reduction in LDL-C of 60% for Lipfendra compared to an increase of 3% for placebo at week 24 (95% CI: -62, -57%).
  • Statistically significant reductions in secondary endpoints from baseline to week 24 compared to an increase of 3% for placebo:
    • 54% mean reduction in non-HDL-C for Lipfendra;
    • 50% mean reduction in ApoB for Lipfendra.

• At week 24, in the CORALreef HeFH trial, treatment with Lipfendra resulted in:
  • A statistically significant and clinically meaningful reduction in LDL-C of 59% compared to placebo (95% CI: -66, -53; p<0.001), with a reduction from baseline (primary endpoint) in LDL-C of 58% for Lipfendra compared to an increase of 3% for placebo;
  • Statistically significant reductions in secondary endpoints from baseline to week 24 compared to an increase of 2% for placebo:
    • 52% mean reduction in non-HDL-C for Lipfendra;
    • 48% mean reduction in ApoB for Lipfendra.

In CORALreef Lipids, the frequencies of adverse reactions in adults with hypercholesterolemia were similar between those treated with Lipfendra and those receiving placebo. Similar proportions of Lipfendra-treated patients and placebo-treated patients discontinued treatment because of an adverse reaction. In CORALreef HeFH, the most common adverse reactions in adults with HeFH treated with Lipfendra that occurred at higher frequencies compared to placebo were diarrhea (Lipfendra 7%, placebo 2%) and dizziness (Lipfendra 9%, placebo 4%). Similar proportions of Lipfendra-treated patients and placebo-treated patients discontinued treatment because of an adverse reaction. The safety profile observed in adults with HeFH in CORALreef HeFH was otherwise generally consistent with that observed in adults with hypercholesterolemia in CORALreef Lipids.

About CORALreef Lipids and HeFH

CORALreef Lipids (NCT05952856) was a Phase 3, multicenter, double-blind, randomized, placebo-controlled study in which 2,904 patients with hypercholesterolemia (including those with and without HeFH) and a history of a major ASCVD event or increased risk for development of a first major ASCVD event were randomized in a 2:1 ratio to receive Lipfendra 20 mg orally once daily (n=1,935) or placebo (n=969) for 52 weeks. Patients required additional LDL-C reduction despite stable lipid-lowering treatment with moderate- or high-intensity statins (unless statin intolerance was documented) with or without other lipid-modifying therapy. Patients taking PCSK9 inhibitors were excluded from the trial. The primary efficacy outcome measure was the mean percent change from baseline to week 24 in LDL-C.

CORALreef HeFH (NCT05952869) was a Phase 3, multicenter, double-blind, randomized, placebo-controlled study in which 303 patients with HeFH were randomized in a 2:1 ratio to receive Lipfendra 20 mg orally once daily (n=202) or placebo (n=101) for 52 weeks. Patients required additional LDL-C reduction despite stable lipid-lowering treatment with moderate- or high-intensity statins, with or without other lipid-modifying therapy. The diagnosis of HeFH was made by clinical criteria or genotyping. The primary efficacy outcome measure was the mean percent change from baseline to week 24 in LDL-C.

https://en.wikipedia.org/wiki/Enlicitide_chloride

FDA Approves Lipfendra (enlicitide) Oral PCSK9 Inhibitor to Reduce LDL-C in Adults with Hypercholesterolemia

Study links semaglutide and tirzepatide to fewer anxiety and depression diagnoses in obesity care

IN CONTINUATION OF MY UPDATE ON semaglutide and tirzepatide 

In a recent study published in the journal Communications Medicine, a group of researchers examined associations between initiation of tirzepatide or semaglutide and incident neuropsychiatric diagnoses in adults with obesity, compared with other weight-loss treatments, with separate analyses for individuals with and without type 2 diabetes.

Background

Currently, obesity affects more than 650 million adults globally, with implications for physical and mental well-being. People with obesity are more likely to suffer from psychiatric conditions, including anxiety and depression, than people without obesity. Moreover, mental illness can increase the chances of developing obesity. Newer incretin-based medications like semaglutide and tirzepatide have changed obesity treatment by producing substantial weight loss, but their effects on neuropsychiatric health remain uncertain in routine clinical practice. 

About the study

Researchers conducted a retrospective cohort study using de-identified electronic health records from the TriNetX United States Collaborative Network between January 2020 and November 2025. Adults meeting the study’s obesity criteria, who newly initiated tirzepatide or semaglutide, were identified and compared with matched individuals who started naltrexone-bupropion, phentermine, or phentermine-topiramate. The study included two separate analyses based on whether or not the participants had type 2 diabetes, and bariatric surgery recipients and a non-pharmacological weight-loss cohort were also evaluated as contextual comparison groups.

To increase comparability between treatment groups, propensity score matching was performed using demographic features, body mass index (BMI), glycated hemoglobin (HbA1c), medical history, co-existing treatments, healthcare utilization, and results of laboratory investigations. Patients with type 1 diabetes, prior bariatric surgery, history of organ transplantation, human immunodeficiency virus (HIV) infection, and end-stage renal disease were not included. Patients were monitored for a maximum of 24 months from treatment initiation until the initial diagnosis of a neuropsychiatric outcome, death, loss to follow-up, or end of study.

The primary outcome was a new diagnosis of anxiety disorder. Secondary outcomes included diagnoses of depression, mood disorder, insomnia, broadly defined cognitive deficits, nerve disorders, peripheral neuropathy, and substance-related disorders. Hazard ratios with 95% confidence intervals (CIs) were obtained using Cox proportional hazards models, adjusted for possible confounders, and various sensitivity analyses were also performed.

Study results

Before matching, individuals initiating incretin-based therapies differed considerably from comparator groups, particularly regarding psychiatric illnesses and psychotropic medication use. After matching on propensity scores, the groups had very similar baseline demographic characteristics, cardiometabolic health issues, laboratory measures, and health care use, allowing for more reliable comparisons between the treatment groups.

 

Individuals receiving semaglutide and tirzepatide generally had lower hazards of several recorded neuropsychiatric diagnoses when compared to bariatric surgery recipients.

Among individuals with obesity and type 2 diabetes, both medications were associated with lower hazards of anxiety disorders, broadly defined cognitive deficits, mood disorders, and depression. Similar results were seen for individuals without type 2 diabetes, but the neurological outcomes were less consistent between the groups. 

Semaglutide was associated with a higher hazard of nerve disorders in participants without diabetes, while tirzepatide showed lower hazards of substance-related disorders and peripheral neuropathy compared with bariatric surgery. The negative control analyses did not find any clinically meaningful differences, providing some reassurance about the analytical approach.

Compared with naltrexone-bupropion, semaglutide was associated with lower hazards of anxiety disorders, depression, cognitive deficits, and insomnia in adults with type 2 diabetes. Tirzepatide also showed lower hazards of anxiety disorders, depression, mood disorders, and cognitive deficits within this group.

Similar reductions were observed among adults without diabetes, indicating that both medications were consistently associated with lower rates of several recorded psychiatric diagnoses than this comparator.

Among adults without type 2 diabetes, a direct comparison between tirzepatide and semaglutide showed that tirzepatide was associated with higher hazards of anxiety disorders and insomnia than semaglutide, while no consistent differences were observed for most neurological outcomes after statistical adjustment. However, the authors noted that absolute and relative estimates differed for anxiety and insomnia in this head-to-head comparison, so these small differences should be interpreted cautiously.

Absolute risk differences indicated larger reductions in anxiety disorders among individuals with type 2 diabetes than among those without diabetes when tirzepatide or semaglutide was compared with naltrexone-bupropion.

Sensitivity analyses generally supported the primary findings. Per-protocol and as-treated analyses showed similar directions of association for anxiety and depression, although the strength of some associations varied depending on treatment persistence. Lower use of psychiatric medications, particularly selective serotonin reuptake inhibitors (SSRIs), was also observed among incretin-based therapy recipients compared with matched comparator groups.

Subgroup analyses suggested that the associations were generally consistent across age, BMI, and clinical characteristics, with some stronger associations observed among older adults and individuals with severe obesity.

Exploratory analyses generally showed greater reductions in body weight and HbA1c over 24 months in the incretin-based therapy groups than in the conventional anti-obesity medication groups, although some comparisons varied by diabetes status and outcome measure.

Additional sensitivity analyses using stricter outcome definitions and alternative cohort criteria yielded findings that were directionally similar, though some estimates became less precise due to smaller sample sizes. Importantly, cognitive findings were sensitive to outcome definition, and the broad cognitive endpoint included codes that could reflect acute or transient altered mental status rather than dementia or progressive cognitive decline.

Conclusion

The findings suggest that initiation of tirzepatide and semaglutide is associated with different neuropsychiatric outcome patterns depending on the comparator treatment and the presence of type 2 diabetes. Compared with naltrexone-bupropion, both medications were generally associated with lower hazards of anxiety and depression. In contrast, tirzepatide showed higher hazards of anxiety and insomnia than semaglutide among adults without type 2 diabetes.

These findings provide clinicians and patients with important real-world evidence to inform treatment decisions, while underscoring the need for continued patient monitoring. However, the results should not be interpreted as evidence that these medications prevent dementia, progressive cognitive decline, or psychiatric disease, because the study relied on diagnosis codes and remains vulnerable to residual confounding and misclassification.

In addition, as this study was observational, prospective studies with standardized neuropsychiatric assessments are needed to confirm these associations. Further research is needed to understand how these medications may influence mental health outcomes across different patient populations.

Study links semaglutide and tirzepatide to fewer anxiety and depression diagnoses in obesity care

Bacteria's 'mix-and-match' code could create new cancer-fighting drugs

A team of researchers at the University of Warwick and Monash University has solved a puzzle that has stumped drug developers for decades: how bacteria naturally create multiple versions of powerful cancer therapies. The breakthrough could accelerate the development of new treatments for hard-to-treat cancers.

Harnessing bacterial enzymes to create drug variants, a strategy known as combinatorial biosynthesis, has long been a goal for scientists. But without understanding how these enzymes interact, progress has stalled.

 

Romidepsin, sold under the brand name Istodax

https://en.wikipedia.org/wiki/Romidepsin

Published in Nature Communications, the researchers have finally revealed how bacterial enzymes communicate and work together to assemble a family of related anticancer compounds. This family includes romidepsin (Istodax), a clinically approved blood cancer treatment. By understanding this "mix-and-match" process and replicating the principle in the lab, the researchers have established an approach to designing new therapies.

How the enzymes coordinate

"For decades, we've known that bacteria can naturally produce multiple versions of powerful anticancer drugs, yet we had no idea how they achieved this," said first author Dr. Munro Passmore, a research fellow in the Department of Chemistry at the University of Warwick.

"This work finally cracks that code. We've identified how the different enzymes communicate and cooperate to produce these drug variants, something that has eluded researchers because the system is so elegantly economical. It's the breakthrough we needed to actually engineer these drugs ourselves."

The team's analysis reveals that small molecular regions, termed "docking domains," act as connectors between the core drug assembly machinery and the variable component-building enzymes. Crucially, these docking domains use a conserved connection point that is compatible with multiple different enzyme partners, a feature that explains how bacteria generate structural diversity while keeping their drugs precise and effective.

 

A blueprint for new candidates

The work also traces how these drug-producing systems evolve naturally. The researchers found that the newly discovered compound likely evolved from a related drug-producing system through gene duplications and recombinations.

Greg Challis, Monash Warwick Alliance professor of sustainable chemistry at the University of Warwick and Monash University, concluded, "This research gives us a blueprint to do what nature does, but better and faster. By reverse-engineering nature's evolutionary logic, we can now design synthetic pathways that generate new anticancer drug candidates with properties optimized for clinical use, such as superior potency, improved selectivity and fewer side effects.

"Our immediate goal is to build an expanded library of candidates for various cancers where new treatments are urgently needed. This discovery is moving us from understanding how the systems work to building new ones."

 

 

Bacteria's 'mix-and-match' code could create new cancer-fighting drugs

AbbVie bags EC approval for Maviret to treat acute HCV infection

AbbVie announced that the European Commission approved Maviret (glecaprevir/pibrentasvir), an oral pangenotypic direct-acting antiviral (DAA) therapy for the treatment of acute hepatitis C virus (HCV) infection in adults and children aged 3 years and older. With this approval, Maviret is now the only treatment approved in the European Union for both acute and chronic HCV infection.

"More than 12 million people in Europe live with hepatitis C, underscoring the need for earlier treatment," said Roopal Thakkar, M.D., executive vice president, research and development, chief scientific officer, AbbVie. "Today's European Commission approval of Maviret for acute hepatitis C infection enables earlier intervention, aiming to help more people access curative therapy at the time of diagnosis, while accelerating progress toward the goal of eliminating hepatitis C as a public health threat."

HCV is a highly infectious blood-borne disease that often goes undetected because people may not show symptoms. While HCV is curable, many people remain undiagnosed. If left untreated, HCV can progress to severe liver complications, including cirrhosis and end-stage liver disease. Current clinical guidance supports treating nearly all people with acute or chronic HCV infection.

"People living with HCV infection frequently face delayed treatment, leading to loss to care and onward transmission," said Massimo Puoti, MD, director of the Infectious Diseases Department at Niguarda Hospital in Milan, Italy. "With this approval, healthcare professionals across the European Union now have an approved treatment option to treat patients at the earliest stage of infection, supporting prompt intervention and helping to reduce transmission, disease progression, and long-term complications for people living with hepatitis C."

Globally, HCV poses a substantial health and economic burden, with over 200,000 deaths each year from liver cancer. People living with HCV are up to 17 times more likely to develop liver cancer than those unaffected.

The approval was supported by data from the Phase 3, multicenter, single-arm prospective study evaluating the safety and efficacy of Maviret eight-week treatment regimen in patients with acute HCV infection.

The study results showed Maviret to be a highly efficacious treatment for people with acute HCV. The majority of the adverse events reported were mild or moderate in severity. The most common adverse events were fatigue, diarrhea, headache, and asthenia.AbbVie continues to collaborate with global regulatory authorities to support access to Maviret for people living with acute HCV infection. Maviret is approved in the United States, Saudi Arabia, New Zealand, Canada, Taiwan, Australia and Argentina for the treatment of acute and chronic HCV infection in adults and children aged 3 years and older.

The overall safety profile observed in the M20-350 study was similar to that observed in patients with chronic HCV infection. No serious adverse reactions or adverse reactions leading to treatment discontinuation that were judged as treatment-related were observed among patients with acute HCV infection. The most commonly reported adverse reactions were fatigue (3%), asthenia (2%), headache (2%), and diarrhea (2%).

https://en.wikipedia.org/wiki/Glecaprevir/pibrentasvir

MORE : AbbVie bags EC approval for Maviret to treat acute HCV infection

Sanofi announces approvals for Wayrilz and Cenrifki

The Japanese Ministry of Health, Labor and Welfare (MHLW) has granted marketing and manufacturing authorization to French pharma major Sanofi’s (Euronext: SAN) Wayrilz (rilzabrutinib), a novel oral reversible Bruton’s tyrosine kinase inhibitor (BTKi).

The drug is authorized for the treatment of persistent or chronic immune thrombocytopenia (ITP) in patients who do not respond sufficiently to other treatments or in whom tolerability is considered to be problematic. Wayrilz can help address the underlying causes of the disease, through multi-immune modulation, targeting key pathways across the immune system.

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Tolebrutinib

https://en.wikipedia.org/wiki/Tolebrutinib

Wayrilz (rilzabrutinib)

https://en.wikipedia.org/wiki/Rilzabrutinib

Sanofi announces approvals for Wayrilz and Cenrifki

Tea Plants' Secret Weapon Against Disease: The Power of Sakuranetin

Tea plants use sakuranetin as a natural antifungal shield against anthracnose, offering hope for greener farming Tea, one of the world's most cherished beverages, may have a powerful natural defense system hidden within its leaves

Scientists from the Zhejiang Academy of Agricultural Sciences have uncovered a molecular mechanism that enables certain tea plants to resist anthracnose—a destructive fungal disease that causes significant losses in tea plantations worldwide.

Their research reveals that a naturally occurring compound called sakuranetin (SAK) acts as a potent antifungal shield, helping resistant tea varieties stop infections before they spread.

The findings, published in Horticulture Research, provide fresh insights into how tea plants defend themselves and could open new avenues for sustainable tea cultivation. 

Understanding Tea Plant Resistance

Anthracnose, caused by the fungus Colletotrichum camelliae, is among the most damaging diseases affecting tea crops. The pathogen spreads through wind and rain, infecting leaves and reducing both yield and quality.

Current control methods rely heavily on synthetic fungicides, raising concerns about environmental impact and chemical residues in a beverage consumed globally as a direct infusion.

Although tea plants naturally produce defensive compounds such as catechins and caffeine, researchers wanted to understand how the plant activates additional defenses after a fungal attack.

To investigate, the team compared two tea cultivars with contrasting disease responses: 'Zijuan', which is naturally resistant to anthracnose, and 'Longjing43', a widely cultivated but more susceptible variety.

The Science Behind Sakuranetin

The researchers discovered that when C. camelliae attacks, the resistant cultivar 'Zijuan' rapidly produces high levels of sakuranetin, a plant defense molecule known as a phytoalexin. This compound creates a hostile environment for the fungus, significantly restricting its growth.

Laboratory tests revealed that sakuranetin displayed stronger antifungal activity against C. camelliae than epigallocatechin gallate (EGCG), one of tea's most abundant and well-known catechins.

The key to this defense lies in an enzyme called naringenin 7-O-methyltransferase (NOMT), produced by the CsNOMT gene. The enzyme converts a flavonoid precursor, naringenin, into sakuranetin, effectively equipping the plant with a powerful chemical weapon.

Researchers observed that infected 'Zijuan' leaves accumulated substantial amounts of sakuranetin, whereas the susceptible cultivar 'Longjing43' produced very little.

A Molecular Relay Activates the Defense

The study uncovered an intricate defense pathway controlled by the plant hormone jasmonic acid (JA), a key regulator of immune responses in plants.

When the fungus invades, JA signaling becomes activated. This, in turn, stimulates a transcription factor called CsMYC2.1, which binds directly to the promoter region of the CsNOMT gene and switches it on.

Once activated, CsNOMT boosts sakuranetin production, creating a rapid chemical barrier against fungal invasion.

Researchers describe this process as a molecular relay:

Pathogen attack → JA signaling → CsMYC2.1 activation → CsNOMT expression → Sakuranetin production → Antifungal defense

This cascade was considerably stronger in 'Zijuan' than in 'Longjing43', explaining why the resistant cultivar is better protected from anthracnose.

Experiments Confirm the Protective Role

To confirm the importance of this pathway, scientists altered the expression of the CsNOMT gene.

When CsNOMT was silenced, sakuranetin levels dropped and plants became more vulnerable to anthracnose infection. Conversely, increasing CsNOMT expression elevated sakuranetin production and significantly reduced disease symptoms.

These experiments demonstrated that disease resistance is not determined by the presence of a single gene alone, but by how efficiently the plant activates its entire defense network when challenged by a pathogen.

Implications for Sustainable Tea Farming

The discovery has important implications for the future of tea cultivation.

The genes CsNOMT and CsMYC2.1 could serve as molecular markers, allowing breeders to identify and develop anthracnose-resistant tea varieties more quickly through marker-assisted breeding.

In addition, sakuranetin itself may provide a blueprint for developing natural biopesticides or plant defense stimulants that reduce reliance on synthetic fungicides.

Such approaches could help tea growers improve crop resilience while addressing growing concerns over environmental sustainability and chemical residues.

Beyond Tea: A Broader View of Plant Immunity

The findings also broaden scientists' understanding of plant immunity. While phytoalexin-based defenses have been extensively studied in crops such as rice and model plants, this research demonstrates that woody perennial crops like tea also rely on inducible chemical defenses to combat disease.

By linking hormone signaling, gene regulation, metabolite production, and disease resistance into a single framework, the study offers one of the clearest pictures yet of how tea plants mount a sophisticated defense against fungal attack.

For tea lovers around the world, this hidden molecular shield may one day help ensure healthier crops, more sustainable farming practices, and a more resilient future for one of the world's most beloved beverages.

Ref : JA–CsMYC2.1–CsNOMT–sakuranetin module contributes to differential anthracnose resistance in Camellia sinensis - (https://academic.oup.com/hr/article/13/5/uhag022/8444634?login=false)

https://en.wikipedia.org/wiki/Sakuranetin

More: 

Tea Plants' Secret Weapon Against Disease: The Power of Sakuranetin

FDA Approves Baxfendy (baxdrostat) as the First Aldosterone Synthase Inhibitor Treatment for Adults with Hypertension

AstraZeneca’s Baxfendy (baxdrostat) has been approved in the US as a first-in-class aldosterone synthase inhibitor (ASI) for the treatment of hypertension in combination with other antihypertensive medications, to lower blood pressure in adults who are not adequately controlled.

• Approval based on BaxHTN Phase III results showing statistically significant and clinically meaningful reduction in systolic blood pressure in patients with uncontrolled or resistant hypertension
• Baxfendy 2mg lowered systolic blood pressure by 15.7 mmHg (9.8 mmHg placebo- adjusted) from baseline in BaxHTN trial

There are 1.4 billion people worldwide living with hypertension.¹ In the US, approximately 50% of patients living with hypertension who are already taking multiple antihypertensive medications still struggle with persistently elevated blood pressure,² which is a leading risk factor for cardiovascular disease and premature death.^3,4 Hypertension is the most prevalent and significant modifiable cardiovascular risk factor worldwide, accounting for more deaths and disability than any other modifiable risk.^5-7

Baxfendy is a first-in-class, highly selective and potent ASI designed to lower blood pressure in a new way by specifically inhibiting the production of aldosterone,⁸ a hormone that raises blood pressure to unhealthy levels and increases the risk of heart and kidney problems.^9-11

The approval by the US Food and Drug Administration (FDA) was based on positive results from the BaxHTN Phase III trial,¹² with Baxfendy demonstrating statistically significant and clinically meaningful seated systolic blood pressure reduction at both 2mg and 1mg doses in patients with uncontrolled and resistant hypertension on two or more medications. Baxfendy was generally well-tolerated with no unanticipated safety findings.

Dr. Bryan Williams, Chair of Medicine at University College London, and BaxHTN primary investigator, said: “We have been waiting for an innovative medication like Baxfendy for hypertension for many years. Its novel way of lowering blood pressure has the potential to transform clinical practice by targeting a root cause of persistently uncontrolled hypertension. In addition, the nearly double-digit placebo-adjusted systolic blood pressure reduction achieved with Baxfendy is exciting and clinically meaningful for clinicians and patients. Epidemiological data indicate that a 10 mmHg decrease in systolic blood pressure is associated with a roughly 20% lower risk of serious cardiovascular events.”

John M. Clymer, Executive Director, National Forum for Heart Disease & Stroke Prevention, said: “Hypertension remains a staggeringly widespread silent killer and a leading risk factor for stroke, heart attack, kidney damage and dementia. Tens of millions of people struggle to control their blood pressure despite lifestyle changes and currently available treatments. Innovative, new treatments could help millions protect their heart, kidney and brain health.”

Ruud Dobber, Executive Vice President, BioPharmaceuticals Business Unit, AstraZeneca, said: “The approval of Baxfendy offers a much‑needed, first-in-class innovation for people living with persistently uncontrolled hypertension who have not responded to or tolerated existing medicines. In the US, about 23 million patients are uncontrolled despite being on two or more medicines for hypertension, which is a disease that has seen little therapeutic progress for the past two decades.”

In the BaxHTN Phase III trial,¹³ published in the New England Journal of Medicine,¹² Baxfendy (baxdrostat) demonstrated statistically significant and clinically meaningful efficacy for the treatment of patients with hypertension on top of standard of care. At week 12, the absolute reduction from baseline in mean seated SBP was 15.7 mmHg (95% confidence interval [CI], -17.6 to -13.7) and placebo-adjusted reduction was 9.8 mmHg (95% CI, -12.6 to -7.0; p<0.001) for the 2mg dose. For the 1mg dose, the absolute reduction from baseline was 14.5 mmHg (95% CI, -16.5 to -12.5) and placebo-adjusted reduction was 8.7 mmHg (95% CI, -11.5 to -5.8; p<0.001). The reduction in mean seated SBP with placebo was 5.8 mmHg (95% CI, -7.9 to -3.8). Results were consistent across both uncontrolled and treatment-resistant subgroups.

https://en.wikipedia.org/wiki/Baxdrostat

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FDA Approves Differin Epiduo Acne Gel (adapalene/benzoyl peroxide) for Nonprescription Use in the Treatment of Acne

In continuation of my update on Adapalene

Galderma (SIX: GALD), the pure-play dermatology category leader,  announced   the United States (U.S.) Food and Drug Administration (FDA)  approval of  Differin Epiduo Acne Gel (Adapalene 0.1% and Benzoyl Peroxide 2.5% Acne Treatment) for over-the-counter (OTC) use in ages 12 years and older, marking a significant Prescription-to-OTC transition in acne care.

Adapalene

• unique Prescription-to-OTC switch in acne care, this approval expands access to a dermatologist-trusted, prescription-strength treatment for millions of acne sufferers ages 12 years and older
• Backed by more than 15 years of real-world dermatologist use and a robust clinical research program, this milestone demonstrates the depth of science behind the Differin and Epiduo heritage
• Adapalene plus benzoyl peroxide (0.1/2.5%) was the first FDA-approved, stable, fixed- dose prescription acne treatment to combine of benzoyl peroxide with a retinoid, and is now available over-the-counter
• The formulation is engineered to target multiple causes of acne more effectively than either of its individual active ingredients alone

This milestone represents yet another example of Galderma’s unique Integrated Dermatology strategy, demonstrating how proven innovations from its Therapeutic Dermatology portfolio can further strengthen its Dermatological Skincare offerings. The Prescription‑to‑OTC transition highlights Galderma’s scale and expertise in successfully commercializing dermatology innovations across the full spectrum of acne care.

With the approval of Differin Epiduo OTC, Galderma is bringing its proven acne science to a broader population of acne sufferers through wider access to a dermatologist-recommended, prescription-strength treatment, while further strengthening its global leadership in acne care.

Delivering continued innovation in acne prevention and care

Differin Epiduo is a topical acne treatment that combines adapalene, a third-generation retinoid originally discovered and developed by Galderma to address the stability and tolerability challenges of earlier retinoids, with benzoyl peroxide (0.1/2.5%). This adapalene molecule reflects Galderma’s long-standing leadership in retinoid science, delivering an innovation-led approach that goes beyond traditional OTC acne actives. Together, these two dermatologist-trusted ingredients address key biological drivers of acne – clearing clogged pores, killing acne-causing bacteria, and reducing acne inflammation – to help clear acne, prevent future breakouts and improve skin tone, texture, and overall appearance.^1,2

The formulation is further powered by its Simulgel™ Gel Base, which stabilizes and evenly distributes both active ingredients while maintaining benzoyl peroxide’s efficacy and improving overall tolerability. This enables a simple, one-pump, once-daily regimen – a level of ease that is critical to building consistent routines and achieving clearer skin over time.

“This approval marks an important milestone in acne care and reflects Galderma’s longstanding leadership in acne and retinoid science. Differin Epiduo pairs two complementary, evidence‑based actives: adapalene, a highly stable and well‑tolerated retinoid developed by Galderma, and benzoyl peroxide, a proven antimicrobial agent. This retinoid-benzoyl peroxide combination aligns with dermatology guidelines, which strongly recommend using both together as a first‑line, multimodal approach to acne treatment. Bringing this scientifically grounded combination to the OTC setting allows us to extend that legacy to patients across the U.S. while preserving the clinical rigor that underpins its effectiveness.” BILL ANDRIOPOULOS, PH.D., HEAD OF GLOBAL MEDICAL AFFAIRS, GALDERMA

Clinical data supporting the approval demonstrated:

• Proven efficacy across multiple randomized, controlled Phase 3 studies, with adapalene/benzoyl peroxide gel consistently outperforming adapalene alone, benzoyl peroxide alone, and vehicle gel across inflammatory, non-inflammatory, and total acne lesions, as well as Investigator Global Assessment (IGA) success rates (“clear” or “almost clear”).^3-5
• Clinically meaningful improvement in lesion counts seen as early as Week 1, with antimicrobial activity beginning on Day 1 and up to 70.3% reduction in inflammatory acne lesions at Week 12.³
• Sustained efficacy with long‑term use, maintaining ~65% total lesion reduction in a single arm study through 12 months, which supports once‑daily, ongoing acne control.⁶
• Proven efficacy across diverse patient populations, with consistent results and favorable tolerability across skin tones.

“This milestone reflects a meaningful advancement for patients, as it expands access to a clinically proven, dual-active acne solution without the need for a prescription. In my practice, the combination of easy access and a simple, once-daily application can help patients use treatment more consistently in their treatment journey for the best possible outcomes.” HEATHER WOOLERY-LLOYD, MD, BOARD-CERTIFIED DERMATOLOGIST, UNITED STATES

First approved as a prescription treatment, Epiduo^® (Adapalene 0.1% and Benzoyl Peroxide 2.5%) Gel has been trusted by dermatologists for more than 15 years, with millions of prescriptions written worldwide. Its global clinical legacy includes more than ten Galderma studies involving over 3,200 patients, along with extensive third-party studies, across a wide range of ages, skin tones and acne severity. With this Prescription-to-OTC switch, Galderma continues to play a defining role in shaping modern acne care, leveraging its own proprietary science to advance dermatology, and expanding access to effective treatments.

Differin Epiduo will be available over-the-counter at most major retailers, including Walmart, Ulta, Target and Amazon, beginning in the summer of 2026. With a commitment to providing effective solutions across consumers’ acne journey, the Differin portfolio also includes cleansers, treatments, and moisturizers to support and provide wholistic solutions. For more information on Differin Epiduo and other Differin products, please visit www.differin.com and join the Differin community on Instagram, Facebook and YouTube to stay up to date on the latest innovations.

https://en.wikipedia.org/wiki/Adapalene

FDA Grants Accelerated Approval to Hepcludex for HDV

Gilead Sciences, Inc. (Nasdaq: GILD)  announced  the U.S. Food and Drug Administration (FDA)  granting  accelerated approval for Hepcludex (bulevirtide-gmod) 8.5 mg for the treatment of adults living with chronic hepatitis delta virus (HDV) infection, making it the first and only approved treatment for HDV in the United States.

• Chronic HDV is considered the most severe form of viral hepatitis due to rapid disease progression towards liver failure and liver-related death
• Approval introduces the first FDA-approved therapy for this disease with limited treatment options and high unmet need

The FDA granted accelerated approval to Hepcludex based on reductions in HDV RNA and normalization of alanine aminotransferase (ALT), supported primarily by data from the pivotal, controlled Phase 3 MYR301 study. At Week 48, the study demonstrated a statistically significant improvement versus the control (delayed treatment) group in a combined virologic and biochemical response. Improvement in disease-related clinical outcomes has not been established. Continued approval for the approved indication may be contingent on verification and description of clinical benefit in a confirmatory trial.

Chronic HDV is considered the most severe form of viral hepatitis and is associated with a markedly higher risk of rapid disease progression, liver failure, and mortality compared with HBV alone. In the United States, studies in general populations have estimated that HDV affects between 2% and 4% of individuals who have chronic hepatitis B virus (HBV), representing ~40,000-80,000 people.

“Hepatitis delta virus is associated with rapid progression of liver disease and a high risk of serious or even life-threatening liver-related complications,” said Dr. Ira Jacobson, MD, Department of Medicine at NYU Grossman School of Medicine. “For patients, an HDV diagnosis means managing two distinct viral liver diseases—hepatitis B and hepatitis D—each contributing to disease progression, monitoring demands, and treatment complexities. The approval of Hepcludex for chronic HDV represents a critical advancement, introducing a long-awaited option that begins to address a significant unmet medical need and has the potential to meaningfully alter the course of this devastating disease for people living with HDV in the United States.”

MYR301 (NCT03852719) evaluated the efficacy and safety of Hepcludex in adults with chronic HDV, with treatment administered for up to 144 weeks followed by 96 weeks of off-treatment follow-up. Hepcludex met its primary endpoint at Week 48, with continued treatment, demonstrated sustained efficacy and was generally well tolerated through up to 144 weeks of on-treatment exposure.

“The approval of Hepcludex represents a historic milestone for people living with HDV in the United States, marking the first FDA-approved treatment for HDV,” said Dietmar Berger, MD, PhD, Chief Medical Officer at Gilead Sciences. “This reflects years of close engagement with the FDA and the application of rigorous science to address a serious disease with long-standing unmet need. With Hepcludex, we now have the opportunity to deliver a meaningful clinical advancement that has the potential to change the trajectory of HDV for patients in the U.S.”

U.S. Access and Hepcludex Approval Across Markets

The Gilead Support Path^® Program offers information and resources to help patients diagnosed with chronic HBV, HDV and hepatitis C virus (HCV) and primary biliary cholangitis (PBC), as well as healthcare professionals, understand coverage and financial options for prescribed Gilead treatments.

Bulevirtide 2 mg is also approved for use in the European Economic Area (EEA) and other countries globally to treat people living with chronic HDV.

Please see below for U.S. Indication and Important Safety Information for Hepcludex.

U.S. Indication for Hepcludex

Hepcludex (bulevirtide-gmod) 8.5 mg for injection is indicated for the treatment of chronic hepatitis delta virus infection in adults without cirrhosis or with compensated cirrhosis.

This indication is approved under accelerated approval based on a decrease in HDV RNA and alanine aminotransferase (ALT) normalization. An improvement in disease-related clinical outcomes has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

https://en.wikipedia.org/wiki/Bulevirtide